August Q&A - Episode 299

Welcome to the Gladden longevity podcast with Dr. Jeffrey Gladden, where our passion is helping you to become an AJ hacker. On this show, we want to help you optimize your life energy, longevity, health and human performance with impactful and actionable information by answering four questions. How good can we be? How do we make 100 the new 30? How do we live well beyond 120? And how do we live young for a lifetime? Now here's today's episode of the Gladden Longevity Podcast. Welcome to the Gladden longevity podcast with Dr. Jeffrey Gladden, where our passion is helping you become an age hacker. On this show, we want to help you optimize your life energy, longevity, health and human performance with impactful and actionable information by answering five questions. How good can we be? How do we make 100 the new 30? How do we live well beyond 120? How do we live young for a lifetime? And how do we develop a. A 300 year old mind? I'm Steve Reiter and Dr. Gladden. We're back for another monthly Q and A. Yeah.

Excited to, to do it with you. Good to see you, Steve.

Good to see you too, my man. So how's your August gone thus far?

It's been pretty amazing, actually. Lots of cool things and we're actually in this podcast, we're going to talk about some of the stuff that I've got coming up. So even next week. So it'll. It's going to be a good August all the way through.

Next week. Well, the first topic we're going to talk about is proteomic organ age, blood tests, and the pace of aging markers. I've never heard of an organ age test.

Yeah, me.

Right. So we're, we're theoretically answering listeners questions. But I will tell the audience that I took poetic license here and wanted to share with you things that I think you'll find interesting to hear about. And the first one is to understand that of course, we're a mosaic of many ages. You've heard us talk about that on the podcast before. And every organ really has its own age, if you will.

Really. I mean, I think about that when I think of someone who's drank their entire life. Obviously their liver is going to be older, if you will, than the rest of their body and I'm sure other organs. But I didn't really realize that my kidneys could be older than my liver or my heart.

Absolutely, absolutely.

Yeah.

No, every organ system is kind of a standalone, you know, down to bone, skin, muscle, and then the internal organs you know, all the internal organs, pancreas, liver, kidneys, adrenal glands, stomach, GI tract, colon, heart, lungs, and then brain, of course, and the nervous system in general, which is another really, really interesting area. You know, one of the things that we've been doing is, as we've been doing functional testing, to look at those organ systems, like, what is your VO2 max? You know, what are your liver parameters based on blood testing, what are your kidney parameters based on blood testing? And we go about that with more comprehensive panels than most people, certainly in general, medicine, would do. And yet beyond that is another layer of kind of peeling back the onion on what is the age of your organs. And so with DNA methylation testing, Truage Diagnostics is the company that we've been using, they will give you organ system ages for about 11 or 12 different organs, your brain, your heart, your kidneys, your liver, your lungs, things like that. And what they're doing is they're looking at DNA methylation patterns that are reflective of those organs and then essentially estimating the age of that organ, and then they give you a composite age of all of those organs. Right. So you get the composite age and then you get the breakdown per organ system, which is interesting. If you peel the onion back a little bit further, you can actually look at protein markers in the blood, which is referred to as proteomics. And, and so now you've moved outside the nucleus of the cell where the DNA methylation patterns are being identified, and now you're looking into the cytoplasm of the cells, and in the blood, it's the plasma itself. And you're looking for proteins and those proteins, the configuration of those proteins, the number of proteins that there are of particular types will create a picture of what the underlying organ status is, or age is in this case. Right. So, and what's happening is they're, they're looking at these protein profiles compared to these large cohorts of people where they've collected this in the past. So, for example, there's a. In the UK, there's a biobank that has about 45,000 individuals in there. And so they can compare your protein signature profile to 45,000 other people to give you an idea kind of where you stand in the. Against the general population.

Right.

And it turns out that it can be helpful for identifying problems prior to them sort of showing up. And there's, there's a new test that we're excited to get our hands on. It's not here yet. I talked with the CEO of The company last week actually email and he tells me that the lab, they're a company out of India called Tzar Tzar. He tells me that the lab in the US is going to open up in Denver. They, he said they were getting ready to sign some agreements and then they need to kind of build it out. So hopefully this fall, of course I've been told it'll be in three months about six times. But that being said, when that comes online, they have a test called an all organ biopsy that's now looking at a combination of proteomics and transcriptomics, which are the messenger RNA signals that come off of the DNA. And combining those two things with some DNA profiling, et cetera, to give you what they call an all organ biopsy where you can go in and through that technology also get a status update on each organ system. And if you're really serious about longevity, then it's important to understand that you're really only as young as your oldest age.

Right.

So you really want to know what is the status of each organ. It's kind of like, you know, building a company. You want to know the status of each department, how well is it performing, or if you've got a race car, for example, you want to know what each of the component status is because your car's only going to be as good and durable and fast as the weakest component. So same is true for us. And so it's really exciting to me to see that testing is really rapidly moving in this direction. Now the omics testing right now, the proteomics I was emerg talking about, there is a, a group out of Stanford apparently called Vero V E R O slash Teal Vero Steel Omics that has research partnerships. And those tests are going to be around $1,000 probably to get things done. To look at your organ age, the all organ biopsy test is going to be five or six thousand dollars to get that done, from what I understand. So these tests are not necessarily inexpensive, but they are remarkably proficient at characterizing not only a status, but in the case of TSAR actually telling you things you might be headed towards, like are you headed towards dementia, are you headed towards a heart attack, are you headed towards a stroke, are you headed towards developing cancer for that matter. And so getting that sort of preemptive information becomes really very powerful. So this is one of the reasons we're so interested in it. And then of course there is many people have heard about the pace of aging. This was popularized by Brian Johnson with the Longevity Olympics, where he was using one particular parameter, the rate of aging, if you will, that came out of a town in New Zealand called Dunedin, D U N E D I N Dunedin, and it was called the Dunedin Pace Trial. They ran a trial over there in New Zealand to see how people were aging. And from that they looked at DNA methylation patterns and developed this clock, if you will. So you can see in a chronological year how much you're aging. Are you aging more than one year when you go through a chronological year, or are you aging less than one year? And so this is also nice to superimpose on top of these omic ages, if you will. So the bottom line is that we're getting better at and actually understanding where somebody is in the aging process, which, of course is the first thing you've got to know if you're going to make the, you know, if you're going to make the race car race longer or faster or better. Right. So. And then there's a lot of things that can be done if you find that there are many lifestyle interventions or many supplements and things that you can modify depending on the findings. And. But it's a really, really cool area.

I don't know.

I don't know how that strikes you as every man on the call here, Steve, but it's pretty, pretty intriguing. We're doing a lot of the testing. I mean, we're doing all the testing now. And in fact, some years ago, I developed a proteomic and transcriptomic test to look at this very thing related to the hallmarks of aging. It's just that at that point in time, it was prohibitively expensive to do it. It was almost like 4 became almost like 14 or $15,000 to do a test. And it was just like, you know, nobody can really justify that. So it's nice to see that things are progressing and getting cheaper.

Yeah.

So how much is that looking to be in terms of being tested now that things are getting cheaper?

Yeah. So it's going to be, you know, you right now, if you want to do a true diagnostic test and you want to do a combination of several of their tests, it's. I don't have the exact numbers in front of me, but you can probably get that done for, I'm going to say, and interpret it and gone through and everything for around a thousand dollars. Right. So it's not.

Wow, okay.

Yeah.

That's a significant drop from the 1415 that you had developed.

Well, it's a little bit different. It's a little bit of a tangential test to what I was developing. The other tests that are being developed, though, seem to be sort of shaving some expense off of that. But I was doing both proteomics and transcriptomics, which is looking at RNA and proteins both. Right. And the tests that we've been talking about are just proteomics only. Right. So they're going to be cheaper just by default. But even with that, they're getting cheaper, even the proteomics are getting cheaper.

Right.

So now we're down around maybe $1,500, something like that, so.

Yeah.

Yeah, so it's good stuff.

So what excites you about this? And practically, how do you see this helping people in their health journey?

Yep. So practically there are two sides of the coin. One is my headed towards a cliff? I don't know, I'm headed towards. This is a. This, is this a way to identify that and which organ system is involved in that? Is it your immune system, is it your cardiovascular system, is it your brain? All those things can be answered. And as the testing is refined, particularly with the TSAR testing, we'll be able to see, is it Alzheimer's, is it Parkinson's, is it a stroke versus a heart attack? You know, these kinds of things. So there's even more precision in knowing what cliff you might be headed towards. The second reason it's really important is if you're not headed towards a cliff, you may be looking towards a cliff. Right, Right. You're not running towards it, but you're kind of pointed in that direction. That's helpful because if you can intervene sooner, you can steer yourself away from that, even looking in that direction, let's say.

Right.

And if, certainly if you're running towards it, there's a lot that can be done to slow that down or go the other way to where you're running away from it. Right. So that's the power of knowing. There are lots of interventions we can do to do that. Then the other thing is that for the people that are really looking to optimize their longevity through their lifestyle and supplements and sleep and the trackers, the wearables and things and all the things that they're doing, the question becomes, well, geez, I'm doing all this. How well is it working out?

Right.

How good am I doing? And am I putting the energy, time, attention and resources into the things that matter the most? And so this gives you an idea to see what matters most and adjust your, your interventions to make sure you're addressing the things that are most important. As you keep the other things going forward. So it's positive all the way around, as I see it.

Yeah, yeah. Sounds incredible. So the next topic you wanted to talk about was senolytics and multidrug gerotherapy.

Yeah.

Rapamycin and tremitinib.

Well, it's dasatinib and quercetin is one. Those are two medications that people have heard about. But let's talk about. Let's. And fisetin is. Is on there as a nice analytic, about 20 milligrams per kilogram per day. So you can get your weight, take your weight divided by 2.2, that's your weight in kilograms, and multiply by 20 milligrams. And now you've got a dose of how much fisetin. You might want to take two days in a row. And that's. You have to be taking it every day, and you might want to repeat that every couple months. Okay. But what's helpful in pruning senescent cells is, is again with new testing that we have. There's a new test called Sapir P16 that looks at senescence in the immune system. There's a UCLA test that looks at the anatomy of the immune system to give you an idea of senescence. Also from the true age DNA methylation, they will give you a snapshot of your immune system and how youthful or senescent it may be. So we have ways. And then there's another test that can be done that looks at beta galactosidase, which is not the most perfect marker for senescence, but it does give you kind of a ballpark feeling of what's going on. And so that's interesting also. So if you have an idea that your senescence, all burden is building up as it does as we age. And of course, these are the zombie cells that simply take up space and don't really function. So it's like having a company with 100 employees and 20 of them show up to work senescent. It means they're taking up space, but they don't do anything. So the productivity of the company goes down. But then when they become secretory, now they're secreting these inflammatory cytokines into the environment, and now they start recruiting other employees to become senescent. So they stop working, and then they're turning off the lights and the wi fi and locking the doors and making it difficult for the people or the cells or the individuals in this analogy who still are not senescent. It makes it very difficult for them to work properly. And so this is a big part of why aging is an exponential process, right? Because it's a downward spiral. And you can see that if you had a company and now you have 20 and then you have 30, and then 35 and then 38 and then 40 employees that are in this scenario and the lights are off, you can see the company is just going to crater.

Right?

I mean, the productivity is going to crater, literally. So that's what aging is. And so being able to actually prune these senescent cells, fire these people from the company, right. So that they leave is very important. And in doing so, you're starting to turn down the inflammation that goes along with aging. And the inflammation is driving more oxidative stress at the cellular level, which is also very damaging to the underlying, you know, functioning parts of the. Of the cell and other cells that are working properly. So it's a real kind of a cleaning house kind of scenario. Now, what we found is that we really like the P16 Ink 4. A test that I mentioned was Sapir Bio S A P E R E. It's great. And it can actually be treated by taking SGLT2s. It's been shown to actually reverse that. These are diabetes medicines that basically stop glucose from being reabsorbed through the. Through the tubules in the kidneys. And you excrete the glucose into the urine, which can lower blood sugar. It's also been found, so it's used for diabetics. But then it was found that it's actually good for heart disease, it's good for arterial disease. And now it's being shown to actually be good at rebooting the immune system from senescence back to an active immune system.

Right.

Which is super important. And the reason having an active immune system that's not senescent is so important is because it's your immune system that's out there. The natural killer cells are actually pruning senescent cells for you. So as you make the immune system more youthful, you now start to actually do for yourself what previously you were asking the supplements to do. And you're also scavenging for tumor cells when they show up, and you're killing those before they actually take hold and develop actual cancer.

Right.

So when you think about people that make it past 100, they really have three things in common. They have really robust immune systems, they have very good cardiovascular systems, and they actually have very resilient brains.

Right.

And those seem to be. I mean, there are other things, of course, as well, but those three seem to really be central.

So what, what is kind of the drivers of having robust immune system, cardiovascular, healthy brain as you age?

Yeah.

Is it genetic? Is it lifestyle? Is it a combination of those two? Is it something else?

Well, there's always a genetic component to everything, but lifestyle plays a role. You know, the more inflamed you are, the more infections that you face, the more times your immune cells have to divide. And every time they divide, those telomeres inside the immune cells get shorter. So the immune system is very susceptible to telomere shortening. And I hadn't mentioned telomere shortening yet, but I was about to when you asked the question, so I'll mention it.

Now.

When telomeres get short, being able to re lengthen telomeres right through things like TA65 or Isagenix or TAM818 or now hyperbaric oxygen therapy, if you want to wear a mask for 90 minutes a day, five days a week has been shown. Brian Johnson showed he reversed telomere lengths for himself. There are other therapies out there now, looking at gene therapies where they insert the T E R T gene into the cell using an adenovirus vector and they put it into the cell, not into the nucleus, but into the cytoplasm of the cell. So now you're making more telomerase, which is the enzyme that re lengthens telomeres. And that's interesting also. So the point is that there are things to re lengthen telo, but equally important is removing things that are shortening telomeres. You can't re lengthen what you're actively shortening.

Right.

So the first thing to do is to stop shortening the telomeres. Well, how do you do that? Well, one is you, you know, if you've got chronic allergies, if you've got chronic infections, if you've got mold, if you've got Lyme, if you've got, you know, gut issues that are keep you chronically inflamed. Your immune system is dialed up all the time. It's working overtime, and those telomeres are shortening and it's getting weaker and it's much more prone to become senescent earlier. I don't know if that helps answer your question, but that's a big piece of it, the lifestyle piece and the chronic infections, things you're exposed to.

Right.

So, yeah. So the interesting thing about the senescent cells is when they occur and they start to secrete these inflammatory cytokines we can measure Those, we can measure 6 and TNF Alpha.

Right.

And HSCRP. All of those are indicators. And then there are other ways to help with this system. So what we do is we will use a senolytic system like say fisetin, and we'll take it and then we'll do. In fact, I'm going to do a plasmapheresis on Monday. I'll probably take some fisetin over the weekend for two days prior to, prior to this plasmapheresis because I'm going to be basically killing off senescent cells. I just got a test back from true age in June and I don't have a lot of senescent cells and I did the Saphir P16 test and I have a very useful immune system. Like incredibly youthful.

Right.

Like a lot of naivete in my immune system. Not a lot of over committed cells. So my immune system is useful in the sense that it can adapt to new challenges.

Right.

So I'm gonna.

How do you determine that?

Through the testing. Through the testing? Yeah, you do the tests. So anyway, I'm gonna take some fisetin over the weekend and do plasmapheresis. Well, why would you do that? Well, it's great because if you're gonna go in and kill these senescent cells, you're gonna basically dump a bunch of gunk into the system.

Right.

You do plasmapheresis, you take all of that out. Plasmapheresis is when you hook yourself up to the machine and you're pulling blood out of one arm. You run it through a large centrifuge which separates the cells. Right. The red cells and the white cells and the platelets, they sink to the bottom as the centrifuge spins and then the plasma rises to the top. Well, in the plasma is where all those inflammatory cytokines and proteins are. So you throw that away. And we can throw away three liters at a time.

Right.

And replace it with saline and albumin. We can do that safely. And so when you do that, it's almost like now you've killed off the bad guys and now you've got cleaned out the system and then literally seems.

Like quite a bit.

It is quite a bit. It's almost like a full oil change.

Right.

If you're going to donate plasma, you can only donate 200cc's at a time, but you can donate two times a week.

Right.

So you, you replenish your plasma quickly.

But this seems 3 liters with you is significantly more than.

That's right. That's my Point I'm putting it in perspective. It's a lot more than 200ml. Would be 5, 5 of those in a liter, right. So this would be 15 times that.

Yeah.

But it has the ability to actually really clean the system.

Right.

If you're going to clean the system, you clean the system and then the body rejuvenates very quickly.

Right.

And so anyway, this is a really, really powerful scenario. And when we're working with people that are, let's say they've sold a company and they leverage their health to kind of get it, get it across the finish line.

Right.

And they know it. They've been burning midnight oil and they're stressed and they're, you know, they haven't been eating well, haven't been able to exercise and all that stuff. Their body is full of these senescent cells. And we can go in and through a series of these, right. Like maybe doing this every month or six weeks for three, four, five, six sessions. You can actually really start to reboot somebody. Whereas it would take them years to try to reboot what we can do in a matter of months using something like this. And then of course there's other interventions with lifestyle changes and teaching them to manage stress and other things. Anyway, it's a really, it's a great hack to be able to kind of go in and salvage somebody as well as for people that are doing well to intermittently, you know, maybe every quarter or every four months or something like that, three times a year, doing this to kind of keep them, to keep them young.

Right.

So.

Yeah.

So the idea then is to clear out the bad stuff and then rebuild.

That's it. That's it. You don't want to try to rebuild in the middle of a mess. And this is also true if you're going to be doing regenerative theory therapies with stem cells or exosomes or. Yeah. Embryonic, you know, placental or cord blood factors or you know, whatever. You have access to PRP for matter platelet rich plasma, which is full of different signaling molecules. So there are many regenerative tools out there. But those regenerative tools, my analogy for that is that those are like Olympic swimmers, right? And if you put those Olympic swimmers into a swimming pool that's full of, you know, lawn chairs and, and, and logs and sticks, branches from trees that have fallen in there, they're not going to be able to do a very good job. In fact, if you take stem cells and you put them into a petri dish with Somebody, an older person's plasma, they die. They don't do anything. They die. Okay. And if you put them into the plasma of a young person, then they start to actually do their work. Wow. Isn't that interesting? Yeah, yeah. So you really want to, if you're listening to this, it's so important. If you've got a problem and you're thinking about, oh, I want to fix my knee, my hip, or, you know, I'm thinking about getting a stem cell procedure even for your skin, for your face or whatever else, or, you know, my doctor wants to do exosomes. Okay, that's great. But if you haven't cleaned out the swimming pool.

Right.

You're not going to get nearly the results that you would if you sort of sequence it properly where you actually prune the senescent cells, take out the trash, and then start to, you know, put in the rejuvenation factors and then support those rejuvenation factors with other factors. Right. The right supplements for the indication, the right peptides for the indication, you know, that kind of thing. So.

Yeah.

Well, the next topic that you wanted to talk about, big in the news right now, GLP1s. But this is GLP1s as Geronimo Therapeutics Beyond Weight Loss. We know about GLP1s for weight loss.

Yep.

But this was kind of interesting as something else you could use it for.

Yeah. So GLP1s, in my mind, have really turned into a mixed bag. They have really turned into a mixed bag. So when GLP1s were introduced, they were introduced basically to aid with diabetes control. Right. So they would. A GLP1 agonist would go in, and when you take in sugar, incretin comes in. GLP1 comes in. GLP1 causes glucagon to go to work, but it also boosts insulin release.

Right.

So that all of a sudden now you're. You're managing the sugar that came in better than you would have otherwise. And so that was the theory behind them. But then they discovered that the GLP1s were actually having a beneficial effect on heart disease, that people were less prone to heart attacks, that their arteries were doing better.

Right.

And that their kidney function was improving because diabetics, you know, always have kidney compromise. And they started to find that the protein that was leaking in the urine was going down and that the trajectory of kidney loss was changed. They were losing kidney function at a slower rate or they were maintaining kidney function and not losing it at all. In some cases actually reversing kidney functioning, having kidney function improve. And so, right. So all of a sudden it's like, wow, these, these GLP1s are having a lot of, let's call it off target effects that are very useful. And then it started to be shown that, you know, they, they could decrease appetite. So then they were scooped up as weight loss drugs.

Right.

And there are a number of them out there. Ozempic and is probably, you know, kind of the hallmark GLP1. And then there are other combinations of GLP1s and GIPS, which are little different peptides. These are peptide drugs by the way. They again modulate the same system. Madrano is one. And the deal here is that they will decrease appetite and hunger and they'll decrease, they'll also slow gastric emptying. The downside to these drugs when they're used for weight loss or when they're used at all is that you can develop pancreatitis, you can develop gastric stasis right where the stomach doesn't empty. And what we find, people come to us all the time that are taking GLP1s, or we have people that come in and they want to start a GLP1. So we'll start a low dose GLP1 for them very cautiously. And what we've seen as we've looked at mixed populations of people is that people are losing weight, but they're losing muscle preferentially. And the fat that they're not really losing much in the way of fat. Because when you're, when you're starving, so to speak, not getting enough calories, fat is not enough to sustain you. Fat is simply calories. But the body needs other things. It needs minerals and it needs vitamins and things like that that are inside muscle cells. So when you're fasting like a three day fast, a five day fast, we had a guy come in here, was on a 14, no, an 18 day fast water fast. We measured his, right. And he just did this on his own without, without asking us. But he came back in and we measured him. He'd lost a ton of muscle and not very much fat at all. And bone density goes down for these people. So we think that GLP1s, while they are good at sort of modulating appetite, the weight loss is not really constructive weight loss. It's really our idea of weight. It has to do with actually body composition. Like we don't care what people weigh. What we care about is what their muscle mass is and what their body fat is. And you can be 200, you can be 6 foot and 200 pounds and have a, you know, percent body fat of 8 and be in amazing shape. Or you can be 200 with a percent body fat of, you know, 30.

Right.

And be in terrible shape. So it's not about the weight, it's really about what's the composition of the body. So we see that the GLP1s, when they're used for weight loss, many times are used too long and too high dose and leading to what I would call unhealthy weight loss.

Right.

So it's a big problem. There are better ways out there to lose weight. There's a drug, not a drug, there's a supplement called Mimeo. M I M E O Mimeo. M I M. Maybe it's M I M. Yeah, I think it's I IO Maybe that's it. I was trying to think there was an I in there. Yeah, Mimeo. So Mimio, which basically has several components in it, has a bit of niacin. So if you take too much niacin, it'll give you diarrhea. So just know that I've done it and it's happened. But if you take two or three, you should be okay. And different people's GI tracts are more or less susceptible to it. But it also has oea and pea, and oea basically decreases appetite and PEA decreases inflammation in the brain. And that supplement works remarkably well. You can actually dial in your appetite suppression based on how many capsules you take. You take one, you're not going to feel much. You take two, you feel a little bit. You take three, it's yeah, I'm feeling not really that hungry. You take four, it's like, no, I'm not really hungry at all. So you can actually dial in appetite suppression that way as a way to kind of retrain yourself. And the other thing that's super helpful is to do a five day fast mimicking diet, which is actually a kit that's been designed by Prolon. And in that kit you are fasting, quote unquote, for five days, but you're actually eating at the same time, which sounds paradoxical. How can I be eating and fasting simultaneously? Well, what they've done is they've orchestrated these meals, quote, unquote meals to be such that you do a couple of things. One, you get in nutrients that your body needs so you're not having to pull for muscle. Two, they're giving you a little bit of carbohydrate so that you don't have to pull from muscle either. So they've shown that with a five day fast mimicking diet, you're not actually losing muscle or bone density. This has been studied. So that's very interesting. But what you are doing is you are pulling from fat cells. You are also changing insulin resistance, you're also resetting your gut biome, you're also changing your taste buds, you're shrinking your stomach, so you're, you're decreasing your appetite. And at the end it can be a good way to jumpstart into a body composition optimization program where now you're going to take mimeo, you're going to do a fast mimicking diet, maybe initially, maybe once a month for three months or so until your system gets regulated. But we feel like that's a much healthier way. That being said, there is a role for GLP1s and there's microdosing of GLP1s which seems to give a lot of the benefits in the longevity space, brain health and things like that. But without all the appetite suppression and all the side effects. Right. So it's about a tenth of the dose of a normal GLP1. So to go full circle on the GLP1s, I think they still have a role, certainly a role for diabetics and I think they still have a role in longevity. It's just that when they're used for weight loss, I think they're actually being counterproductive. Interesting, huh?

So the idea is microdosing GLP1s to get that heart, kidney, cardiovascular benefits.

That's right. And they're also showing now that it helps in osteoarthritis. There's some new studies related to that cardiovascular disease, as I mentioned. So it's pretty interesting.

So that's fascinating because with everything I've heard about women and even some men developing osteoporosis, using it to lose weight, that a micro dose, you can get the benefits of the good stuff without getting hit with the bad.

That's right. You know, you know there's, I forget who said this, but it was said a long time ago. But you know, everything is medicine or everything is poison. It's just a question of the dose.

Right?

Yeah. Interesting.

All right.

Gene therapy and partial epigenetic reprogramming. Osk.

Yeah.

So this is pretty fascinating. So as I mentioned earlier, you know, we were talking about inserting Tert, the gene Tert into the cytoplasm of the cell. Well, it turns out you can actually insert several different genes. You can insert Clotho, a Clotho gene to increase Clotho production We can actually measure Clotho in clients. There's a couple different ways to do that. And then you can also insert. You can insert Follistatin, which actually keeps you from breaking down muscle.

Right.

Which is interesting. And there's some other genes that are being used also to help optimize longevity and body composition, if you will. So that's one approach to, you know, genetic quote unquote, reprogramming to optimize youthfulness as we age. The Japanese scientist, Dr. Yamanaka, discovered that he could reprogram the epigenetic age of a cell by activating four different genes. And if he activated those four genes inside of a cell, when he left them activated long enough, the cell would return to a pluripotent stem cell. This is when the Nobel Prize was awarded for this back in 2012ish, I think it was. And we all heard about the fact that, oh, my gosh, you can make a stem cell out of a skin cell. Do you remember that when that was on the news?

Yeah.

Yeah.

That's an induced pluripotent stem cell. It's induced by activating the Yamanaka factors to create a pluripotent, which means it can become anything stem cell. So the problem with the Yamanaka factor activation is that when you're activated, you actually increase your risk of cancer because the cells de. Differentiate enough that they kind of lose track of what they are.

Right.

And so now not only can they become anything, but they can also become cancerous. So they figured all this out in mice, and then they took away one of the genes that was the prime culprit. So now they're only using three of these in mice, and they're actually pulsing them on and off. I won't go into the mechanism, but they actually make them sensitive to a typical. To a. To an antibiotic that will either turn them on or off, and doxycycline, I believe. And with that, they could sort of, in the stepwise fashion, make a cell more useful.

Right.

Make a mouse more youthful.

Right.

But they still found if they went too far, that the mice would develop cancer. So that was interesting. Then a paper published in July of 2023 out of David Sinclair's lab at Harvard, who is, you know, one of the major longevity researchers, was really interesting because they hypothesized that they could actually reprogram the epigenetics of a cell in the same way that the Yamanaka factors did. And what they would do is they would use instead of gene therapy, let's call it or gene manipulation. They would just use a combination of medications and supplements. So think of it as chemical reprogramming of a cell. And what they ended up showing was that with a specific combination of valproic acid, which is used for seizure modulation, it's a histone deacetylase inhibitor. And we haven't gotten into that, that's another topic. But it has, it's kind of connected to DNA methylation and then a molecule called C H I R99021. It's a glycogen synthase kinase 3 inhibitor.

Right.

Some of these are anti cancer drugs. Then you've got a Repsox TGF beta inhibitor, which is a direct cancer inhibiting drug. And then you've got another drug called Tran Tranylcycypro. Tranylcypromine T R A N Y L C Y P R O M I N E. It's an MAO inhibitor which is kind of like an antidepressant. Then there's a supplement called Forskolin which is good at increasing cyclic amplify. They combined it also with sodium butyrate and with alpha ketoglutarate and fibroblast growth factors, actually increased by a peptide called BPC150. They were using fibroblast growth factor. So they put together this cocktail and they gave it to mice and they reversed their epigenetic age without having to do any genetic manipulation.

Right. Whoa. Yep.

Isn't that amazing? Yeah. Now the flip side of that coin is that they could. Mice are cancer prone, Right. They're cancer prone mammals. When the mice were taking these, this cocktail, not only did they get younger, they could not give them cancer.

What?

Yes. When they try to inject them with things that they know will give mice cancer, they would, they would laugh it off. They would not get cancer. That's.

Whoa. Right?

That's a freaking game changer.

Tell me about it.

Right.

So I now have in my possession this cocktail and I'm going to start taking it actually. And I'm confessing that here on the podcast, but I've gone to some significant links to kind of pull all that together. I'm really curious and I'll report back on the podcast. Actually, I'm doing testing ahead of time so I can, I'll share with the audience, you know, how this is working. But I think the combination of this with some of the other things. I'm doing the plasmapheresis and I'm also reprogramming the stem cells in the third ventricle of the brain and that are in the wall of the third ventricle of the brain. I'm doing that on Monday and I'm gonna, I've done testing today and I'm gonna do that on Monday in conjunction with plasmapheresis and the analytics. And then I'm going to follow it up with another test to see how that's doing. And then I'm going to layer in the cocktail of molecules. I'm going to see just how, how young can I get, right? Because it's really. The idea is, you know, how good can we be? And yeah, when you look at my organ systems, they're really quite youthful. I mean, when you look at all the markers and you look at. I mean, it's really. I was just going through it with the company today because they had a new test or testing reporting platform and their director of education research was basically saying, gosh, I wish, I wish I had your numbers. I wish I had your profile.

Right?

So it's pretty interesting, but I think is that.

What is that cocktail again?

I just read it off to you. Let me read it off again. You won't be able to get a hold of it. If you, if you're listening to this, it's going to be difficult to pull this together. It's valproic acid, C H I R99021, RepSox, Tranylcypromine, Forskolin, Sodium butyrate, alpha ketoglutarate. Now, those last ones you can get, you can get forskoline online, you can get sodium butyrate, you can get alpha ketoglutarate. Have also been, interestingly enough, forsklen has been shown to improve testosterone. Actually, sodium butyrate, of course, increases fiber in the gut. And alpha ketoglutarate has some longevity benefits on its own. But the magic seems to happen when you combine these things together, as is most things in medicine, right? So you can read about one thing, but it's actually so important as you listen to this to understand it's not just about, oh, he said alpha ketoglutarate, that's the one I can get. I'm going to take that. And by gosh, I'm doing everything I should. I mean, God bless the thought process, but you have to understand there are limitations to that, right? You may be getting 1% of what you would get by doing the whole combination. And this is why it's so important to think about not only the combinations, but the sequencing. And that's why it's so important. Looping back to where we started to do the testing.

Right.

Where are you? What do I need? And how do I orchestrate myself to actually move back the pieces that, you know, are headed towards the cliff. Right. So that's, that's really the key. And that's what we, you know, that's our philosophy here at Glad Longevity. That's how we go about everything. So.

Yeah.

So obviously, as a doctor, medical doctor, and as a researcher, you're able to get some of those compounds that I couldn't get. But what do you think the pricing for? I mean, if this works out for you, do you see yourself bringing this to clients?

I'm always the pointy end of the stick. Right. So if I can. If I can figure out that this is actually working and it's safe and I'm seeing significant changes that corroborate, you know, what other research has been saying, then I will allow other clients once we've done proper testing and, you know, make sure that it's the right thing for them and all that. There's many things, you know, not hoops, but it's just we want to be safe. Right. It's safety first.

Yeah.

And so if we feel like somebody's a candidate, we would let them know that there's a way that they could put this together. Right. So we don't have it inside of a trial currently. And so I'm kind of going outside on. We may bring it into a trial and a way to do that, that might be a next step, but we would, we would diligently work to enable other people to have access to it. Let's just say that. So.

Well, sign me up for that trial.

Okay.

I'm, I. It sounds like a freaking game changer. Absolutely. A game changer.

It is.

And I'd get my ass down to Dallas.

Yeah.

And be there and.

Yeah.

Get some other stuff done while I'm there.

Sure.

Yeah.

No, exactly. It is a process, you know, like, you do want to do the plasma, you do want to go through these steps because it, what it does is it, it makes everything else you do that much more effective and that much better. You need less of the other stuff when you do the right things to get ready for it. Right. It's kind of like, well, I've got a. I've got some bare dirt out in the back of my yard. I'm gonna throw some grass seed out there. It's like, okay, great. Well, you know, as opposed to, I'm going to go out there and till the soil and put stuff in and make the topsoil and get all this and do all that. Then I'll put the seed on, then I'm going to cover it and I'm going to water it and I'm going to do all these things. You know, who's going to get the better yard?

Right.

It's just, it's really the same thing, quite honestly. It's just you're dealing with biology. It's the right sequence, the right preparation, the right understanding. What's my soil need?

Right?

Does it need more phosphate? Does it need more, you know, nitrogen?

What.

You know, what does it need?

Right.

And so you give it that in conjunction. Now all of a sudden you got a bumper crop, right, of either grass or whatever you want to grow. And that's how, that's how we think here as well. So we're just farmers in the end, right? So, yeah.

Final topic, lifestyle science and hormesis. Exercise, sauna, fasting.

Yeah.

Safest effect sizes still come from smartly dosed lifestyle stressors.

Yep.

I think this is. You can never get away from this. So we've talked about a bunch of pretty fancy stuff. We really have. It's pretty fancy and very cutting edge. And yet some of these lifestyle things, exercise, saunas, cold plunges, sleeping. Well, we, you know, you can never get away from that. And, you know, I'll, I'm, you know, we've been on for about an hour. I will just say that, you know, you want to continue to do all the good things that you're doing and if you're not involved with those yet, you want to lean into those, make sure you're getting, you know, cardio is really how you build VO2 max and VO2 max is how you live a long time. Muscle mass is important and you need to build it. And you want strength and you want bone density. From our perspective, we do that in about two days a week. It's the cardio that we focus on and we end up with muscle mass. That's great. And you know, because we're hormonally replete, so we build muscle quickly and. But we also have really high VO2s and, you know, that's the combination that we're going for. And then we use sauna, we use ozone sauna, we use cold plunge intermittently. I don't have a cold plunge here in the office. There's reasons for that. A lot of them had to do with building codes and everything else when we were looking at putting in and it was going to be like a thousand dollar proposition to put in a coal plunge. I'm like, I don't think so. So that being said, we love cold plunge and sauna. The data on Saunders, incredible, right? I mean, 45 reduction, all cause mortality, 50% reduction heart disease, 65% reduction in dementia and Alzheimer's. So using a sauna five days a week, four days a week, actually for 20 minutes at 175 degrees or 180 degrees or the equivalent with an infrared sauna is, you know, it's money in the bank. So all those lifestyle things that you're doing, you know, don't be dissuaded from that. When you hear me talking about some of these special things, that's still the blocking and tackling. And then if you can lay some of these other pieces on top now it gets super exciting. Right? So that's kind of, kind of what we're talking about. Yeah.

Well, Dr. Gladden.

Yes, sir.

Let's finish off August Strong. And if any listeners want to send Dr. Gladden a question, we love answering them here on these monthly calls. Monthly calls. All you need to do is just email us@podcastladdenlongevity.com that's podcastladdenlongevity.com thank you for listening to this week's episode of the Gladden Longevity Podcast. If you would like more information on what we've discussed or other topics, please reference the show notes or go to gladdenlongevitypodcast.com you can also find us on Instagram, Facebook and Twitter by searching Glad Longevity. If you've enjoyed this podcast, please subscribe to get future episodes delivered to you and share our podcast or this episode with someone in your life that you may find benefit. Thank you for listening. We'll be back next week with another exciting episode. The Glide and Longevity Podcast is provided for informational purposes only. It does not constitute medical advice. This content is not intended to be a substitute for professional medical advice, diagnosis or treatment. Always seek the advice of a physician or other qualified health provider with any questions you may have regarding your medical condition. The use of any information and materials linked to this podcast is at the listener's own risk.